DESCRIPTION (Author supplied): This proposed study focuses on fluorescent cell imaging (FCI) in which erythrocyte membranes or leukocyte nuclei from one animal are stained with different fluorescent dyes of different wavelengths, injected systemically in the same animal, excited transcorneally, and tracked and analyzed to quantify blood flow. After imaging fluorescent cells in the blood vessels of the posterior pole of the eye, video frames are analyzed to infer maximum and average blood cell velocities, and relative and absolute volumetric blood flow using an automated data extraction system. The diameters of large ocular blood vessels are measured and mapped. Cell velocities are spectrally analyzed to determine pulsatility. The five objectives of the study are: 1) to establish FCI safety and potential use in humans by performing toxicity tests in rats and monkeys; 2) to develop a statistical framework for comparing parameter maps; 3) to validate FCI by evaluating measurements made in vitro of stained erythrocytes in capillary tubes and in vivo by comparing FCI measurements of velocities and flow rates in the monkey eye to measurements obtained using laser Doppler methods; 4) to compare erythrocyte and leukocyte blood flow velocities in the microcirculation; and 5) to assess the clinical utility of FCI. The fifth goal has four parts. First, FCI will be used to compare blood parameters in a rat model before and after inducing symptoms of diabetes using streptozocin, and in a researcher-blind study, an attempt will be made to use FCI parameter maps to diagnose diabetes. Second, quantification and mapping of blood speeds, pulsatility, and flow rates in the microcirculation of the macula and optic nerve head of a normal monkey will be performed using FCI. Third, those hemodynamic parameters will be mapped in the macular microcirculation of the monkey choroid using FCI. Finally, changes in hemodynamic parameter maps of the monkey eye in response to an acute increase in intraocular pressure will be quantified. With FCI, changes in blood flow rates in diabetic retinopathy and glaucoma might be determined, as well as the effect of consumption of vasoactive drugs.